Inflammation is the foundation for cancer and degenerative/autoimmune diseases. Small changes in diet and exercise, e.g. omega-3 oils, vitamin D, low starch, and maintaining muscle mass, can dramatically alter predisposition to disease and aging, and minimize the negative impact of genetic risks. Based on my experience in biological research, I am trying to explain how the anti-inflammatory diet and lifestyle combat disease. 190 more articles at http://coolinginflammation.blogspot.com

Anti-Inflammatory Diet

All health care starts with diet. My recommendations for a healthy diet are here:

Saturday, September 6, 2008

What’s the point of vitamin C? How is a college athlete sweating in the sun like a speed freak? Are women (or men for that matter) more fertile after a sirloin or a salmon steak? The questions are a bit tricky and they obviously tie into inflammation, so they will need some explanation.

Most plants and animals synthesize their own ascorbic acid, vitamin C, in four steps from glucose. Humans, primates and guinea pigs do not. Vitamin C is used in the conversion of proline into hydroxyproline. Proline is an amino acid that normally punctuates the regular structures of amino acids in proteins so that helices start and stop at the correct points as the linear necklace of a eight hundred amino acids of a protein twists and turns to make a compact, three dimensional enzyme. With the help of vitamin C, collagen proteins made of repeated amino acid triplets containing proline, have a proline in each triplet converted into hydroxyproline. The result of this substitution is that the collagens can now wind around other collagens to form very strong twisted threads that are the foundation of connective tissues. In the absence of vitamin C, the threads form weakly and the resulting connective tissue literally fails to hang together and the result is the symptoms of scruvy: blotchy skin, swollen gums, loose teeth and depression.

I noticed cases of what looked like modern day scurvy in the graphic anti-amphetamine ads on television. It turns out that speed users end up with symptoms that look to me like the defects in connective tissue that I associate with vitamin C deficiency. I think that the speed addicts are suffering from inflammatory depletion of their vitamin C reserves. Amphetamines are rather nasty, because if you take just one dose, your body goes through withdrawal and responds with a sustained burst of the inflammatory cytokine TNF. If you keep taking amphetamines, your body responds with a sustained burst of TNF. Either way you end up wasted.

TNF was originally called cachexin from cachexia, which is the term for the loss of appetite and wasting associated with terminal stages of diseases such as cancer. So TNF is involved in inflammation, which at the cellular level results in the production of enzymes that produce reactive oxygen species (ROS) that would otherwise be useful in protection from pathogens. In a TNF storm all the ROS do is deplete vitamin C. I would expect that someone showing the symptoms of cachexia or amphetamine-induce scurvy might use up ten grams or more of vitamin C a day, if they could get it.

So what about the sun-drenched college athlete? In this case, I suspect that he has a genetic defect in his mitochondria that also results in a depletion of vitamin C. It is not as drastic as the meth-abuser, but still leads to weakened cartilage and sensitivity to the sun. He fails to use sunglasses and the intense blue light on the field further disrupts the mitochondria in the corneas of his eyes. The damaged mitochondria produce ROS and attack the cornea proteins, making them weak and disrupting the optical properties of the surface of the eye. The sun always causes skin damage that can be partially offset by vitamin C supplements. In this case, the daily need for supplements may be several grams of vitamin C per day.

Ascorbic acid is called a vitamin, because it must be present in the diet or a deficiency disease develops. With the increasing prevalence of inflammatory diets and inflammatory lifestyles, production and accumulation of ROS is also increasing. In previous decades connective tissue destruction associated with scurvy was avoided with a couple of hundred milligrams of dietary vitamin C. An anti-inflammatory dose that could also reduce ROS was probably about a gram of vitamin C per day. Nowadays, I think that to have an impact on the chronic inflammation of our obese population the amount of vitamin C may have to be more than doubled and will vary dramatically from person to person.

I haven’t mentioned antioxidants out of simplicity. The ROS are produced by many different processes associated with inflammation and the presence of ROS can also cause inflammation. There are cellular defenses against ROS, i.e. enzymes such as superoxide dismutase and these enzymes are obviously important, because disruption of their functions causes severe diseases, e.g. ALS, and in animal studies increased expression of these enzymes increases longevity. You can also eat your veggies and many of the unusual plant products, e.g. polyphenols, will calm down the reactive oxygen species, i.e. they are antioxidants. But don’t be fooled by the simplicity of the declaration that a plant molecule is an antioxidant. These “antioxidants” interact with dozens of different signaling pathways. That is why all drugs, many of which started out as plant products, have “side effects”.

I finally turn to fertility. Pregnancy requires that the natural inflammation in response to foreign molecules be compromised. In the absence of heightened body-wide inflammation, due to infection, disease, or physical stress, a fertilized egg can locally suppress inflammation and implant. The embryo can continue to suppress inflammation until it is full term, at which time inflammation is enhanced and a baby is born. Chronic inflammation can lead to infertility that is further reinforced by an inappropriate immune reaction to implantation. One treatment for this condition is heparin plus aspirin, both anti-inflammatory.

The introduction of agriculture to human culture led to grain-based diets. This was a dramatic shift from leaves to seeds, which is also from high to low vitamin C, from low to high starch and from high to low omega-3 to omega-6 fat ratios. In essence, this is from an anti-inflammatory to an inflammatory diet. Just as an added interest, this social structure also led to more consistent use of cooking and the production of sugar-amino acid conjugated compounds call advanced glycation endproducts or AGE, which are also highly inflammatory. Does it make sense that agriculture would lead to chronic inflammation? The answer may come from consideration of the impact of inflammation on communicable diseases. Agriculture leads to dramatic increases in population densities and the potential for epidemics. Chronic inflammation inhibits epidemics by enhancing immunity, so human responses of inflammation to the dietary consequences of agriculture are highly advantageous. Chronic inflammation, however, trades resistance to epidemics for increased aging and degenerative diseases.

And finally, what about the salmon? It is provocative to think that agriculture may have reduced the fertility of women until the annual salmon harvest, which brought with it a dramatic increase in the omega-3 fatty acid composition of the diet, a suppression of chronic inflammation and a window of enhanced fertility. Contact with the sea may have been essential for the fecundity of a civilization.

1 comment:

David B
said...

The history of the world in dietary change. I love it. But also the splitting of the population into high carb grain eaters (famers) and lower carb meat eaters (the hunting elites) created physical and mental differences in the population which encouraged castes and class systems to ossify.

This process ebbs and flows through history. We seem to have moved out of nutritionally equal age created by the surpluses of the USA (say 1940 to 1970) to a one in which the poor eat a diet completely different to the enlightened elites and thus find themselves trapped in a state of arrested development.

Listen to my podcast on Jimmy Moore's Livin' La Vida Low Carb Show

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About Me

I grew up in San Diego and did my PhD in Molecular, Cellular and Developmental Biology (U. Colo. Boulder). I subsequently held postdoctoral research positions at the Swedish Forest Products Research Laboratories, Stockholm, U. Missouri -Colombia and Kansas State U. I was an assistant professor in the Cell and Developmental Biology Department at Harvard University, and an associate professor and Director of the Genetic Engineering Program at Cedar Crest College in Allentown, PA. I joined the faculty at the College of Idaho in 1991 and in 1997-98 I spent a six-month sabbatical at the National University of Singapore. Most recently I have focused on the role of heparin in inflammation and disease.